OBJECTIVE To provide reference for medical institutions to establish the record management mode and review rules of off-label use of 5-aminolevulinic acid （ALA） in photodynamic therapy based on the level of evidence. METHODS All ALA-containing outpatient prescriptions in the rational drug use system in our hospital from January 1， 2024 to December 31， 2025 were retrospectively collected. Based on the drug instructions， the current status of off-label use of ALA in photodynamic therapy was identified . The relevant studies in Micromedex， PubMed， CNKI， Wanfang Data and other databases were systematically searched as the relevant evidence-based evidence of ALA off-label use. According to the Off-label Drug Use Filing Standard of the hospital，the evidence-based evaluation method was used to evaluate the evidence-based evidence of ALA off-label use and carry out hierarchical management. RESULTS A total of 1 803 effective prescriptions were included， of which 676 （37.49%） were off-label use， distributed in the dermatology department （564 prescriptions，83.43%） and the plastic surgery department （112 prescriptions，16.57%）. All 676 prescriptions were off-indications medication， involving ten types of skin diseases， primarily including moderate to severe acne （39.94%）， skin warts （25.44%）， Bowen’s disease （11.98%）， and others. According to evidence-based evidence，off-label uses such as moderate to severe acne， actinic keratosis， and Bowen’s disease were managed according to the evidence categoryⅠ orⅡ.The uses of extramammary Paget’s disease and rosacea were managed according to the evidence category Ⅲ.The uses of lichen sclerosus and keloids were managed according to the evidence category Ⅳ.The results of evidence-based evaluation showed that 92.01% of off-label use in our hospital had high-level evidence-based support （ evidence category was gradeⅠ-Ⅱ）. CONCLUSIONS Off-label uses supported by high-level evidence， such as moderate to severe acne， skin warts， and Bowen’s disease， can be managed under filing category Ⅰ or Ⅱ. For the use of lichen sclerosus and keloids， evidence-based evidence is insufficient and should be strictly restricted.The vast majority of ALA off-label use in our hospital has sufficient evidence-based basis.

BACKGROUND:Currently,different methods of model establishment have been derived from different injury modes of spinal cord injury.Traditional physical injury modeling methods have their own advantages and disadvantages,and there is a lack of more effective and stable animal models of spinal cord injury. OBJECTIVE:To establish a reproducible,controllable,trauma-free,low-mortality,more stable,widely applicable,and short-term postoperative care rat model of spinal cord injury. METHODS:Forty Sprague-Dawley rats with similar body mass and ages were randomly divided into a control group and an improved group,with 20 rats in each group.Animal models of spinal cord injury in the control group were constructed using a clip model method,while the improved group used a modified ligation method based on the compression method to make the spinal cord injury models using suture ligation based on fenestration.Postoperative comparisons were made between the two groups,assessing urination behavior,hematuria,pyuria(infection rate),mortality,scoliosis rate and Basso-Beattie-Bresnahan locomotor rating scale scores at 1,3,5,and 7 days after modeling. RESULTS AND CONCLUSION:Compared with the conventional modeling method,the modified ligation method based on the compression method resulted in faster recovery of urination behavior,lower hematuria rate,lower infection rate,lower mortality rate,lower scoliosis rate,and more concentrated and stable Basso-Beattie-Bresnahan scores(all below 2 points within 1 week).This proves that the modified ligation method based on compression is more suitable for the establishment of spinal cord injury models in rats.

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

Objective:To investigate the synergistic activity and mechanism of vinegar baked radix bupleurum polysaccharides(VBCP)in combination with oxaliplatin(OXA),and to provide new ideas for the clinical treatment of primary hepatocellular carci-noma.Methods:MTT assay was used to detect the cytotoxic effect of VBCP 3-4 and VBCP 3-3 in combination with OXA on Huh7 cells;ICP-MS was used to measure the uptake rate of OXA by Huh7 cells and evaluate the in vitro synergistic pathway of VBCP 3-4 in combination with OXA;Western blotting was used to measure the expression levels of related transporter proteins in Huh7 cells and explore the synergistic mechanism of VBCP 3-4 in combination and MRP1 in Huh7 cells,and the protein expression level of multidrug resistance-associated protein(MRP)2 was upregulated to 18.11%and 25.00%,respectively(P=0.008,P=0.001),while that of MRP1 was upregulated to 28.51%(P>0.05)and 39.70%(P=0.015),respectively.After the combination of VBCP 3-4 and OXA,the protein expression of MRP2,MRP1,and breast cancer resis-tance protein(BCRP)was inhibited;MRP2 was reduced by 47.38%in the high-dose combination group(P=0.000)and 15.18%in the low-dose combination group(P=0.049);MRP1 was reduced by 64.96%in the high-dose combination group(P=0.000)and 34.63%in the low-dose combination group(P=0.000);BCRP was reduced by 29.00%(P=0.020)in the high-dose combination group.Acting on Huh7 cells alone,VBCP 3-4 significantly reduced the protein expression levels of MRP2,MRP1,and BCRP,and in the high-dose VBCP 3-4 group,MRP2 and MRP1 were reduced by 24.91%and 20.79%,respectively(P=0.004,P=0.005).VBCP 3-4 downregu-lated the protein expression level of BCRP by 15.02%in the high-dose group(P=0.003)and 13.92%in the middle-dose group(P=0.030).Conclusion:VBCP 3-4 exerts a synergistic effect by inhibiting the expression of the efflux transporter proteins MRP1,MRP2,and BCRP,promoting the intake of OXA by Huh7 cells,and increasing the intracellular effective concentration.

Objective : To explore the central role of interleukin(IL)-25 in allergy of eosinophil asthma. Methods : Forty 4-5 week-old C57BL/6 mice were used in this study(n=10). Mice were randomly divided into 4 groups: WT+shRNA NT group, WT+HDM group, IL-25 shRNA+IL-25 group, and IL-25 shRNA+IL-25+HDM group. According to each group′s treatment requirement, mice were treated with house dust mite and/or IL-25 by intranasal infusion. HE staining and PAS staining were used for lung tissue section staining and pathological analysis. The levels of type 2 cytokines in bronchoalveolar lavage fluid(BALF) were determined by ELISA. Flow cytometry(FCM) was used to determine the number of type 2 helper T(Th2) cells, the group 2 innate lymphoid cells(ILC2) and eosinophils in lung tissues. Mice were treated with FITC-labeled DQ-ovalbumin(DQ-OVA) by intranasal infusion to determine the antigen presentation ability of eosinophils infiltrated in the lungs. Results : HE staining and PAS staining results showed that, compared with WT+shRNA NT group, a large amount of mucus and a large number of eosinophil infiltration were found in the lungs, and subcutaneous thickening of inflammatory airway were observed in the pulmonary vessels, alveolar ducts and the whole alveoli in IL-25 shRNA+IL-25+HDM group. In the IL-25 shRNA+IL-25 group, only a small amount of mucus and a small amount of eosinophil infiltration were found in the lungs, and a small amount of subcutaneous thickening of inflammatory airway were observed in pulmonary vessels, alveolar ducts and the whole alveoli. There was no significant difference in WT+HDM group. Compared with WT+shRNA NT group, the levels of IL-25, IL-4,IL-5,IL-13, IL-33 and interferon-γ(IFN-γ) in BALF significantly increased; the levels of infiltrated Th2, ILC2 and eosinophils in the lung significantly increased; the fluorescence levels of FITC-labeled DQ-OVA in eosinophils infiltrated in lungs significantly increased in IL-25 shRNA+IL-25+HDM group(P<0.05). IL-25 shRNA+IL-25 group mice also showed an increase in the above measurements, but the amplitude were limited(P<0.05). WT+HDM group had no significant difference. Conclusion IL-25 plays an essential role in the allergy and eosinophil antigen presentation processes in eosinophil asthma mice.

To summarize the problems and improvement suggestions in the implementation of GBZ158, the focus groups interview was used to interview industry experts from CDC, Occupational disease prevention and control hospital institutes, employers, third d dd鄄party technical service institutions and universities, and extract their opinions on the problems and improvement suggestions in the implementation of the standard. The operability of GBZ 158 is not strong, and there is a certain overlap with the signs in the fields of firefighting, safety and other fields. It urgently needs to be modified to comply with the reality of occupational health management in China. There are many and concentrated revision opinions on "6. Notification Cards for Occupational Hazards of Toxic Substance in Workplaces" and "7. Setting of Warning Signs in Workplaces with Toxic Substances". It is concluded that Some technical indicators of GBZ 158 have not been according with the current actual work of occupational health, and need to be revised and improved urgently, which includes enhancing the coordination with standards in the fields of firefighting and safety, supplementing normative reference documents, clarifying the setting conditions, scope of use, and application examples of warning signs of occupational hazards.

Objective:By systematically evaluate the implementation of GBZ 2.1, so as to provide technical basis for the future revisions of this standard.Methods:From May to October 2023, Based on the pre survey questionnaire, the semi-structured interview method was used to interviews with experts from CDC, Occupational disease prevention and control hospital institutes, employers, occupational hygiene technical service intermediaries and universities, and the inductive method was used to extract the topics and relevant suggestions.Results:Generally, GBZ 2.1 is scientific, practical, progressiveness and operable. There are still some issues such as OELs overlapping and the correspondence between Chinese and English names. The outstanding problem is the coordination with other standard contents.Conclusion:The technical indicators in GBZ 2.1 could adapt to the needs of current practical work. The coordination between standards needs to be clarified, and the new recommended content needs further promotion and exploration on how to implement it.

Objective To apply the image recognition method based on distance graph convolutional network to the image processing of malaria-infected erythrocytes for realizing the multi-stage recognition of malaria and improving the diagnostic efficiency of malaria.Methods A multi-stage malaria recognition model based on distance graph convolutional network was proposed.A radial basis function was firstly added in KNN graph construction algorithm to construct adjacency matrix and assign weights to the nearest-neighbor nodes according to the similarity between nodes,so as to weaken the effects of the distant nearest-neighbor nodes on the central node.Then,attention mechanism was introduced to update adjacency matrix dynamically in the graph convolutional network for making the model pay attention to near-neighbor nodes with higher similarity,and finally the multi-stage image recognition of malaria-infected erythrocytes was completed.Results Validated on the Malaria-MIT dataset,the experimental results show that compared with original model,the proposed method improved accuracy,precision,recall rate and F1-score to 96.18%,96.23%,96.18%and 96.18%,respectively.Conclusion The proposed approach can effectively accomplish the task of multi-stage image recognition of malaria-infected erythrocytes.

Objective To investigate the effect and potential mechanism of rat mesenchymal stem cells(MSC)on D-galactose-induced brain-tissue aging.Methods A rat brain-aging model was established by injecting D-galactose,and rats in the treatment group received MSC injections via the tail vein.Superoxide dismutase(SOD)activity and malondialdehyde(MDA)levels were assessed in rat brain tissue at the end of the experiment,and pathological changes in brain tissue were observed by hematoxylin-eosin(HE)staining.Expression levels of the inflammatory factors interleukin(IL)-1 and IL-6,the pathway proteins brain-derived neurotrophic factor(BDNF)-tropomyosin receptor kinase B(TrkB),the negative growth regulators p53 and p16,as well as vascular endothelial growth factor(VEGF)and basic fibroblast growth factor(bFGF)were observed by polymerase chain reaction(PCR)and Western Blot.Results Brain levels of SOD activity were significantly increased and MDA levels were significantly decreased in rats in the modle group compared with the treatment group(P＜0.05).The pathological state of the cerebral cortex and hippocampus were improved and the number of neurons and nucleus pulposus ratio in the brain were increased in the treatment group,as shown by HE staining.Expression levels of IL-1,IL-6,p53,and p16 were significantly decreased,while BDNF,TrkB,VEGF,and bFGF were significantly increased in the treatment group compared with the model group,as shown by PCR and Western Blot(P＜0.05).Conclusions These result suggest that MSCs potentially mitigate D-galactose-induced cerebral senescence by concurrently modulating the BDNF-TrkB axis to attenuate oxidative/inflammatory damage,while enhancing the secretion of vasculotrophic(VEGF)and neurotrophic(bFGF)factors for neuronal maintenance.

Objective:To analyze the molecular characteristics of prevalent Bordetella pertussis (Bp) isolates in Liaocheng City, Shandong Province in 2024. Methods:From March to August 2024, oropharyngeal swabs were collected from suspected pertussis cases at Liaocheng People′s Hospital in Shandong Province for Bp isolation. A total of 99 Bp isolates were obtained. Whole-genome sequencing was performed on all isolates, followed by Multilocus Sequence Typing (MLST), vaccine antigen-related gene typing (including ptxP, ptxA, ptxB, ptxC, ptxD, ptxE, fhaB, fim2, fim3, and prn), 23S rRNA gene typing, and phylogenetic analysis. To capture the differences between Bp isolates and vaccine strains in Liaocheng City, the international vaccine strain Tohama I and the Chinese vaccine strain CS were included in the analysis. Antimicrobial resistance testing against 11 agents was performed on 52 isolates. Results:The throat swabs of 99 Bp isolates were collected from patients aged 44 days to 42 years, and the median age of the patients was 7 (5, 8) years. All isolates ptxP were ptxP3 type. 74 isolates (74.75%) carried the prn150, while 21 isolates (21.21%) were prn-deficient. The predominant antigenic profile was ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150, found in 72 isolates (72.73%). All 99 isolates carried the A2047G mutation in the 23S rRNA gene. Antimicrobial susceptibility testing showed that the MICs of macrolides and clindamycin for all 52 Bp isolates were all >256 mg/L. However, the isolates showed low MIC for seven other antimicrobials tested, including trimethoprim-sulfamethoxazole, amoxicillin, and levofloxacin. MLST typing revealed that 94 isolates (94.95%) were identified as ST-2, while 5 isolates (5.05%) belonged to a novel sequence type (ST-118). Phylogenetic analysis demonstrated that all 99 Bp isolates were highly homologous but clustered in evolutionary branches distinct from vaccine strains. Conclusion:In 2024, Bordetella pertussis isolates in Liaocheng City exhibit distinct clonal epidemic characteristics, with the predominant antigenic genotype being ptxP3/ ptxA1/ ptxB1/ ptxC4/ ptxD1/ ptxE4/ fhaB1/ fim2-1/ fim3-1/ prn150. All isolates are resistant to macrolide antibiotics.